fibulin 5


Gene Symbol: fibulin 5
Description: fibulin 5
Alias: A55, DANCE, EVEC, fibulin-5, FIBL-5, developmental arteries and neural crest EGF-like protein
Species: mouse
Products:     fibulin 5

Top Publications

  1. Choi J, Bergdahl A, Zheng Q, Starcher B, Yanagisawa H, Davis E. Analysis of dermal elastic fibers in the absence of fibulin-5 reveals potential roles for fibulin-5 in elastic fiber assembly. Matrix Biol. 2009;28:211-20 pubmed publisher
  2. Nakamura T, Ruiz Lozano P, Lindner V, Yabe D, Taniwaki M, Furukawa Y, et al. DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries. J Biol Chem. 1999;274:22476-83 pubmed
    ..and characterized mouse, rat, and human cDNAs that encode a novel secreted protein of 448 amino acids named DANCE (developmental arteries and neural crest epidermal growth factor (EGF)-like)...
  3. Mitani A, Nagase T, Fukuchi K, Aburatani H, Makita R, Kurihara H. Transcriptional coactivator with PDZ-binding motif is essential for normal alveolarization in mice. Am J Respir Crit Care Med. 2009;180:326-38 pubmed publisher
    ..Furthermore, Taz-heterozygous mice were resistant to bleomycin-induced lung fibrosis. The results indicate the importance of TAZ in lung alveolarization and its involvement in the pathogenesis of lung fibrosis. ..
  4. Horiguchi M, Inoue T, Ohbayashi T, Hirai M, Noda K, Marmorstein L, et al. Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase. Proc Natl Acad Sci U S A. 2009;106:19029-34 pubmed publisher
    ..These data suggest a mechanism of elastogenesis, in which a sufficient amount of FBLN4 is essential for tethering LOX to tropoelastin to facilitate cross-linking. ..
  5. Yanagisawa H, Davis E, Starcher B, Ouchi T, Yanagisawa M, Richardson J, et al. Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature. 2002;415:168-71 pubmed
    ..The molecules and mechanisms involved in this process are unknown. Fibulin-5 (also known as EVEC/DANCE) is an extracellular matrix protein abundantly expressed in great vessels and cardiac valves during embryogenesis, ..
  6. Wieslander C, Rahn D, McIntire D, Acevedo J, Drewes P, Yanagisawa H, et al. Quantification of pelvic organ prolapse in mice: vaginal protease activity precedes increased MOPQ scores in fibulin 5 knockout mice. Biol Reprod. 2009;80:407-14 pubmed publisher
    ..generated recently, both of which have null mutations in genes involved in elastic fiber synthesis and assembly (fibulin 5 and lysyl oxidase-like 1)...
  7. Rahn D, Acevedo J, Word R. Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1351-8 pubmed publisher
  8. Drewes P, Yanagisawa H, Starcher B, Hornstra I, Csiszar K, Marinis S, et al. Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Am J Pathol. 2007;170:578-89 pubmed
  9. Budatha M, Roshanravan S, Zheng Q, Weislander C, Chapman S, Davis E, et al. Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. J Clin Invest. 2011;121:2048-59 pubmed publisher
    ..These results suggest that POP is an acquired disorder of extracellular matrix and that therapies targeting matrix proteases may be successful for preventing or ameliorating POP in women. ..

More Information


  1. Hirai M, Horiguchi M, Ohbayashi T, Kita T, Chien K, Nakamura T. Latent TGF-beta-binding protein 2 binds to DANCE/fibulin-5 and regulates elastic fiber assembly. EMBO J. 2007;26:3283-95 pubmed
    ..We have previously shown that developing arteries and neural crest EGF-like protein (DANCE) (also designated fibulin-5) is essential for elastogenesis by studying DANCE-deficient mice...
  2. Kobayashi N, Kostka G, Garbe J, Keene D, Bachinger H, Hanisch F, et al. A comparative analysis of the fibulin protein family. Biochemical characterization, binding interactions, and tissue localization. J Biol Chem. 2007;282:11805-16 pubmed
    ..Immunoelectron microscopy localized fibulin-4 and -5 to fibrillin microfibrils at distinct locations. Our studies suggest there are unique and redundant functions shared by these structurally related proteins. ..
  3. Wan W, Gleason R. Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation. Am J Physiol Heart Circ Physiol. 2013;304:H674-86 pubmed publisher
    ..Dysfunction in neonatal formation of elastic fibers abrogates many of the changes in mechanical response that take place during the maturation. ..
  4. Segade F. Molecular evolution of the fibulins: implications on the functionality of the elastic fibulins. Gene. 2010;464:17-31 pubmed publisher
    ..Differentiation in gene expression further split Fibulin-5 from the other elastic fibulins, likely contributing to its nonredundant role in elastic fiber assembly. ..
  5. Topalovski M, Hagopian M, Wang M, Brekken R. Hypoxia and Transforming Growth Factor ? Cooperate to Induce Fibulin-5 Expression in Pancreatic Cancer. J Biol Chem. 2016;291:22244-22252 pubmed
    ..These findings offer insight into the signaling axis that induces Fbln5 expression in PDA and a potential strategy to block its production. ..
  6. Wan W, Yanagisawa H, Gleason R. Biomechanical and microstructural properties of common carotid arteries from fibulin-5 null mice. Ann Biomed Eng. 2010;38:3605-17 pubmed publisher
    ..Despite these significant differences fbln5 ?(/)? CCAs exhibited nearly normal levels of cyclic strain over the cardiac cycle. ..
  7. Sullivan K, Bissonnette R, Yanagisawa H, Hussain S, Davis E. Fibulin-5 functions as an endogenous angiogenesis inhibitor. Lab Invest. 2007;87:818-27 pubmed
    ..Taken together, these results suggest that the normal angiogenic process is enhanced in the absence of fibulin-5. ..
  8. Marmorstein A, Marmorstein L. The challenge of modeling macular degeneration in mice. Trends Genet. 2007;23:225-31 pubmed
    ..By modeling MD in mice, we can learn about aspects of MD that an animal with a macula would be unable to teach us. ..
  9. Zheng Q, Davis E, Richardson J, Starcher B, Li T, Gerard R, et al. Molecular analysis of fibulin-5 function during de novo synthesis of elastic fibers. Mol Cell Biol. 2007;27:1083-95 pubmed
    ..These results also support the potential use of fibulin-5 as a therapeutic agent for the treatment of elastinopathies...
  10. Dabovic B, Robertson I, Zilberberg L, Vassallo M, Davis E, Rifkin D. Function of latent TGF? binding protein 4 and fibulin 5 in elastogenesis and lung development. J Cell Physiol. 2015;230:226-36 pubmed publisher
    ..These results are consistent with a role for TGF?2 in lung septation and for Ltbp4 in regulating fibulin-5 dependent elastic fiber assembly. ..
  11. Noda K, Dabovic B, Takagi K, Inoue T, Horiguchi M, Hirai M, et al. Latent TGF-? binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. Proc Natl Acad Sci U S A. 2013;110:2852-7 pubmed publisher
    ..These data suggest a unique function for LTBP-4 during elastic fibrogenesis, making it a potential therapeutic target for elastic fiber regeneration. ..
  12. Turner C, Badu Nkansah K, Crowley D, van der Flier A, Hynes R. α5 and αv integrins cooperate to regulate vascular smooth muscle and neural crest functions in vivo. Development. 2015;142:797-808 pubmed publisher
    ..Analysis of cultured α5/αv-deficient vSMCs suggests that this is achieved, at least in part, through proper assembly of RGD-containing extracellular matrix proteins and the correct incorporation and activation of latent TGF-β. ..
  13. Jaffe M, Sesti C, Washington I, Du L, Dronadula N, Chin M, et al. Transforming growth factor-? signaling in myogenic cells regulates vascular morphogenesis, differentiation, and matrix synthesis. Arterioscler Thromb Vasc Biol. 2012;32:e1-11 pubmed publisher
    ..TGF-? signaling in SMCs controls differentiation, matrix synthesis, and vascular morphogenesis. Effects of TGF-? on SMC gene expression appear to differ depending on the location of SMCs in the aorta. ..
  14. Kapustin A, Stepanova V, Aniol N, Cines D, Poliakov A, Yarovoi S, et al. Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated ?1-integrin-dependent cell migration. Biochem J. 2012;443:491-503 pubmed publisher
    ..We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from ?1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility. ..
  15. Lee Y, Albig A, Regner M, Schiemann B, Schiemann W. Fibulin-5 initiates epithelial-mesenchymal transition (EMT) and enhances EMT induced by TGF-beta in mammary epithelial cells via a MMP-dependent mechanism. Carcinogenesis. 2008;29:2243-51 pubmed publisher
    ..Taken together, these findings identify a novel EMT and tumor-promoting function for FBLN5 in developing and progressing breast cancers. ..
  16. Fu J, Zheng M, Zhang X, Zhang Y, Chen Y, Li H, et al. Fibulin-5 promotes airway smooth muscle cell proliferation and migration via modulating Hippo-YAP/TAZ pathway. Biochem Biophys Res Commun. 2017;493:985-991 pubmed publisher
    ..It may function at least partly through binding to ?1 integrin and modulating Hippo-YAP/TAZ pathway to promote the proliferation and migration of ASMCs. ..
  17. Chapman S, Sicot F, Davis E, Huang J, Sasaki T, Chu M, et al. Fibulin-2 and fibulin-5 cooperatively function to form the internal elastic lamina and protect from vascular injury. Arterioscler Thromb Vasc Biol. 2010;30:68-74 pubmed publisher
    ..The DKO mouse will serve as a unique animal model to test the effect of vessel integrity during various pathological insults. ..
  18. Hou X, Li H, Zhang C, Wang J, Li X, Li X. Overexpression of Fibulin-5 attenuates burn-induced inflammation via TRPV1/CGRP pathway. Exp Cell Res. 2017;357:320-327 pubmed publisher
    ..The results suggest that overexpression of Fibulin-5 attenuates thermal inflammation via suppressing TRPV1/CGRP pathway. This may provide a potential therapy target to alleviate excessive inflammation in burn patients. ..
  19. Feng Y, Valley M, Lazar J, Yang A, Bronson R, Firestein S, et al. SRp38 regulates alternative splicing and is required for Ca(2+) handling in the embryonic heart. Dev Cell. 2009;16:528-38 pubmed publisher
    ..Taken together, our results demonstrate that SRp38 regulates cardiac-specific alternative splicing of triadin pre-mRNA and, reflecting this, is essential for proper Ca(2+) handling during embryonic heart development. ..
  20. Orriols M, Varona S, Martí Pàmies I, Galán M, Guadall A, Escudero J, et al. Down-regulation of Fibulin-5 is associated with aortic dilation: role of inflammation and epigenetics. Cardiovasc Res. 2016;110:431-42 pubmed publisher
    ..HDAC inhibitors or pharmacological approaches that aimed to preserve FBLN5 could be useful to prevent the disorganization of ECM induced by inflammation in AAA. ..
  21. Freeman L, Lomas A, Hodson N, Sherratt M, Mellody K, Weiss A, et al. Fibulin-5 interacts with fibrillin-1 molecules and microfibrils. Biochem J. 2005;388:1-5 pubmed
    ..Fibulin-5 may provide a link between tropoelastin and microfibrils in the pericellular space during elastic fibre assembly...
  22. Schiemann W, Blobe G, Kalume D, Pandey A, Lodish H. Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades. J Biol Chem. 2002;277:27367-77 pubmed
    Fibulin-5 (FBLN-5; also known as DANCE or EVEC) is an integrin-binding extracellular matrix protein that mediates endothelial cell adhesion; it is also a calcium-dependent elastin-binding protein that scaffolds cells to elastic fibers, ..
  23. Spencer J, Hacker S, Davis E, Mecham R, Knutsen R, Li D, et al. Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration. Proc Natl Acad Sci U S A. 2005;102:2946-51 pubmed
    ..These findings demonstrate the importance of the elastic laminae in vascular injury, and reveal an unexpected role of fbln-5 as an inhibitor of vascular smooth muscle cell proliferation and migration. ..
  24. Kuang P, Goldstein R, Liu Y, Rishikof D, Jean J, Joyce Brady M. Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1147-52 pubmed
    Fibulin-5, previously known as DANCE and EVEC, is a secreted extracellular matrix protein that functions as a scaffold for elastin fiber assembly and as a ligand for integrins alphavbeta3, alphavbeta5, and alpha9beta1...
  25. Budatha M, Silva S, Montoya T, Suzuki A, Shah Simpson S, Wieslander C, et al. Dysregulation of protease and protease inhibitors in a mouse model of human pelvic organ prolapse. PLoS ONE. 2013;8:e56376 pubmed publisher
    ..These data collectively suggest that the balance between proteases and their inhibitors contributes to support of the pelvic organs in humans and mice. ..
  26. Noda K, Nakamura T, Komatsu Y. Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice. Biochem Biophys Res Commun. 2015;466:585-91 pubmed publisher
    ..Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. ..
  27. Le V, Stoka K, Yanagisawa H, Wagenseil J. Fibulin-5 null mice with decreased arterial compliance maintain normal systolic left ventricular function, but not diastolic function during maturation. Physiol Rep. 2014;2:e00257 pubmed publisher
    ..We propose that Fbln5-/- mice represent a suitable model for further studies to determine mechanistic relationships between arterial compliance and LV diastolic function. ..
  28. Nguyen A, Itoh S, Jeney V, Yanagisawa H, Fujimoto M, Ushio Fukai M, et al. Fibulin-5 is a novel binding protein for extracellular superoxide dismutase. Circ Res. 2004;95:1067-74 pubmed
    ..This interaction may represent a novel mechanism for controlling vascular redox state in the extracellular space in various cardiovascular diseases such as atherosclerosis and hypertension in which oxidative stress is increased. ..
  29. Consonni S, Werneck C, Sobreira D, Kühne F, Moraes S, Alvares L, et al. Elastic fiber assembly in the adult mouse pubic symphysis during pregnancy and postpartum. Biol Reprod. 2012;86:151, 1-10 pubmed publisher
    ..with genetic modifications of the proteins involved in elastogenesis, such as lysyl oxidase-like 1 (LOXL1) and fibulin 5. During pregnancy, elastic fiber-enriched pelvic tissues are modified to allow safe delivery...
  30. Zheng Q, Choi J, Rouleau L, Leask R, Richardson J, Davis E, et al. Normal wound healing in mice deficient for fibulin-5, an elastin binding protein essential for dermal elastic fiber assembly. J Invest Dermatol. 2006;126:2707-14 pubmed
    ..Clearly, the long-term effect of the absence of fibulin-5 on the function and integrity of regenerated skin needs to be further addressed. ..
  31. Schluterman M, Chapman S, Korpanty G, Ozumi K, Fukai T, Yanagisawa H, et al. Loss of fibulin-5 binding to beta1 integrins inhibits tumor growth by increasing the level of ROS. Dis Model Mech. 2010;3:333-42 pubmed publisher
  32. Lemaire R, Korn J, Schiemann W, Lafyatis R. Fibulin-2 and fibulin-5 alterations in tsk mice associated with disorganized hypodermal elastic fibers and skin tethering. J Invest Dermatol. 2004;123:1063-9 pubmed
  33. Tang J, Xie A, Cai X. [Diverse functions of fibulin-5 in tumors]. Mol Biol (Mosk). 2014;48:875-80 pubmed
  34. Nakasaki M, Hwang Y, Xie Y, Kataria S, Gund R, Hajam E, et al. The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis. Nat Commun. 2015;6:8574 pubmed publisher
    ..These results suggest that Fibulin-5 may be a therapeutic target to short-circuit this profibrotic feedback loop. ..
  35. Wang M, Topalovski M, Toombs J, Wright C, Moore Z, Boothman D, et al. Fibulin-5 Blocks Microenvironmental ROS in Pancreatic Cancer. Cancer Res. 2015;75:5058-69 pubmed publisher
  36. Zhu H, Cabrera R, Wlodarczyk B, Bozinov D, Wang D, Schwartz R, et al. Differentially expressed genes in embryonic cardiac tissues of mice lacking Folr1 gene activity. BMC Dev Biol. 2007;7:128 pubmed
    ..These changes affected normal cytoskeleton structures, cell migration and motility as well as cellular redox status, which may contribute to cardiovascular abnormalities in mouse embryos lacking Folr1 gene activity. ..
  37. Nakamura T, Lozano P, Ikeda Y, Iwanaga Y, Hinek A, Minamisawa S, et al. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature. 2002;415:171-5 pubmed
    ..Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization...